The ability to quantify circulating biomarkers in a timely fashion is crucial for monitoring diseases, organ functions, and drug abuse, so there have been considerable efforts towards developing more convenient and reliable technologies for measuring blood biomarkers. Among the technologies, finger-prick has revolutionized our way to monitor plasma glucose levels in patients with diabetics. However, the technology is highly dependent on readable signals, suitable only for relatively abundant analytes in the serum so far. Most of current methods for measuring circulation biomarkers still rely on blood collection that requires a high level of medical training, as well as time-consuming, labor-intensive blood sample process, storage, and analysis. There are great challenges to develop alternative, rapid, sensitive, and reliable technologies for point-of-care molecular diagnosis.
Recently, microneedle (MN) array-based minimally invasive diagnosis has attracted attention for rapidly detecting blood biomarkers through the skin. Several surface-modified MN arrays have been fabricated, capable of recognizing circulating viral proteins and specific antibodies in mouse dermis, allowing biomarker detection without blood collection and sample processing. Unfortunately, such arrays have two key drawbacks. Concentrations of most blood biomarkers in the upper dermis are too low to be captured by MN arrays. Hence, deep dermal penetration and prolonged application are required to surmount this flaw, which is likely to cause pain, compromising patient compliance. Secondly, there are unacceptably large variations in probe bindings to individual MNs within the same array, due to uncharacterized leakage of biomarkers through capillaries damaged by penetrating MNs. After all, only a few MNs in each array cause such unintended damage and display strong binding, whereas most of the MNs in the array show no or weak capture of plasma biomarkers. Such high variability makes it impossible to quantify multiple biomarkers in one array, or reliably measure a single biomarker for quantity-based diagnosis and/or prognosis.